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1. |
Rapid and Selective Cloning of Monitor Peptide, a Novel Cholecystokinin‐releasing Peptide, Using Minimal Amino Acid Sequence and the Polymerase Chain Reaction |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 1-7
Shin-Ichi Fukuoka,
George Scheele,
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摘要:
cDNA transcripts encoding rat monitor peptide (MP) have been cloned from a A-ZAP-I1 phage library using minimal specific amino acid sequence (six residues), the polymerase chain reaction (PCR), and multivalent PCR probes to distinguish MP transcripts from those that encode a closely related peptide, pancreatic secretory trypsin inhibitor. DNA sequence analysis of 3 cDNA transcripts, MP1-3, revealed the complete amino acid sequence of the prepeptide (79 residues) including an 18-residue hydrophobic signal sequence at the NH, terminus. Sequence divergence in both coding and 3′ noncoding regions indicates a potential exon-exon junction with alternative splicing, which results in a truncated peptide with Arg 58 at the COOH terminus as well as alternative selection of poly(A) signals, respectively. The 5′ nontranslated region of MPl mRNA (282 nucleotides (nt)) contains four upstream ATGs. Conserved structure between MP and anionic trypsinogen mRNAs within 9 nt immediately upstream of the AUG initiation codon may be involved in coupling the expression of MP with anionic trypsinogen, a condition which appears to be required to monitor the intake of dietary protein in the rat.
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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2. |
Establishment of a New Human Pancreatic Adenocarcinoma Cell Line, MDAPanc‐3 |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 8-16
Marsha Frazier,
Sen Pathak,
Zu-Wei Wang,
Karen Cleary,
S. Singletary,
Matilde Olive,
Bruce Mackay,
Peter Steck,
Bernard Levin,
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摘要:
A new cell line was established from a liver metastasis of a human pancreatic adenocarcinoma. The cell line, MDAPanc-3, which arose from a moderately differentiated adenocarcinoma, produces carbonic anhydrase II mRNA, but no detectable levels of insulin or alpha amylase mRNA. The stem line chromosome number was determined to be 43, with six marker chromosomes. Growth of MDAPanc-3 is stimulated by cholecystokinin (CCK) fragment 2633. The cell line will be useful in further studies on the mechanism(s) by which CCK stimulates growth of certain human pancreatic adenocarcinomas and normal human pancreatic exocrine tissue.
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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3. |
Proteolytic Degradation of Human Recombinant Proinsulin/Insulin by Sera from Acute Pancreatitis Patients and Complete Inhibition by Eglin‐C |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 17-26
Paul Lau,
Mark Van Handel,
Mike Larvin,
Michael McMahon,
Michael Geokas,
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摘要:
Sera from patients of biliary, alcoholic, and idiopathic acute pancreatitis with severity scored from 1 to 5 based on the Ranson criteria were tested for proinsulin/insulin degrading activity. Proinsulin degrading activity by normal controls was 8 ± 4% as compared with 22–78 ± 17% with a mean of 45% by the patient sera. An order of magnitude increase of proinsulin degrading activity was accompanied by an order of magnitude increase of immunoreactive pancreatic cationic trypsin(ogen) and (pro)elastase-2 as determined by radioimmunoassay with day 1 sera. Proinsulin degrading activity also showed a negative correlation with the clinical time course and dropped to normal by 6 days after admission. The decrease of proinsulin degrading activity was concomitant with a decrease of serum immunoreactive pancreatic serine proteases. High-performance liquid chromatography analysis of the proteolysis products showed the appearance of insulin and smaller peptides with no proinsulin conversion intermediates. Ninety to ninety-eight percent of proinsulin degrading activity was inhibited by anti-α2-macroglobulin (α2-M) antiserum, or (Ac)Eglin-C(J141), and 52% by an elastase and chymotrypsin-specific inhibitor, MeOSuc-Ala-Ala-Pro-boroVal-pinacol. E64c, TLCK, α1-protease inhibitor (α1-PI), or Trasylol inhibited proinsulin degrading activity by 10–17%, and anti-cathepsin B antiserum by 9%. The observed proinsulin degrading activity did not correlate with the Ranson's scores, age, sex, etiology, total serum immunoreactive insulin, calcium, albumin or α1-M but had a negative correlation with serum α1-PI (r= −0.55) and a positive correlation with serum esterase activity (r= .62). It is concluded that the observed proteolytic activity in the peripheral blood in patients with acute pancreatitis is due to circulating α2-M-bound pancreatic proteases. Fifty-two percent of the activity is due to circulating α2-M-bound elastase and chymotrypsin-like proceases, 10–17% to bound trypsin-like proteases, and 17% to bound cathepsin thiol proteases.
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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4. |
Differing Effects of Ethanol on in vitro Stimulated Pancreatic Enzyme Secretion in Ethanol‐Fed and Control Rats |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 27-36
Daniel Schmidt,
Stephen Pandol,
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摘要:
The single most important risk factor for chronic and acute pancreatitis is the abuse of ethanol, which, theoretically, could affect the pancreas by interacting either with some of its cell receptors or with any of its intracellular signal transduction mechanisms. Therefore, we determined in isolated pancreatic acini from 3 month ethanol-fed rats and controls the dose-response effects of secretagogues on enzyme secretion, both in the presence and absence of ethanol in the incubation medium. In ethanol-fed rats, pancreatic amylase activity was decreased by 40%, compared to controls (with identical carbohydrates intakes), whereas lipase and trypsinogen activities were unaffected. With no ethanol in the incubation medium, basal enzyme releases and enzyme dose-response curves to CCK-8, VIP, secretin, bombesin, and bethanechol were essentially unchanged in ethanol-fed rats compared to controls. In contrast, with 0.1Methanol present in the medium, enzyme responses to VIP, secretin, and CCK-8 were inhibited and that to CCK-8 also shifted to the right in ethanol-fed rats compared to controls. Hence, if rechallenged to ethanol, acini from ethanol-fed rats show inhibited secretions, in response to two secretagogues acting through the release of cyclic AMP, and an inhibited and rightshifted secretory response to CCK.
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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5. |
Effects of TRH on Pancreatic Growth and Secretion in Rats |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 37-41
B. Glasbrenner,
P. Malfertheiner,
L. Duntas,
M. Büchler,
T. Bereiter,
H. Ditschuneit,
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摘要:
Thyrotropin-releasing hormone (TRH) has been shown to be scattered throughout the gastrointestinal tract. High concentrations of TRH are reported in the pancreas of animals and humans. The present study was designed to investigate the pattern of pancreatic adaptation following chronic TRH administration in rats. Ten male Wistar rats were injected daily at 8.00 and 16.00 h with TRH (total dose of 6 mgkg of body weighuday) via a chronic gastric fistula. Ten pair-fed control animals were injected with a saline solution. After 10 days, the rats were killed after an overnight fast; pancreatic wet weight, DNA, protein, amylase, trypsin, and lipase content were determined. Blood TRH levels were measured using a specific RIA (TRH antiserum K2B7, normal range of 30–80 fmol/ml). TRH increased pancreatic wet weight (+ 70%,p< 0.01), DNA content (+83%,p< 0.01), and protein content (+42%,p< 0.05). Pancreatic enzyme concentrations (Ulmg of DNA) were decreased (amylase, −81%; trypsin, −47%; lipase, −59%,p< 0.01). Absolute rates of amylase discharge (U/mg of DNA) in vitro were reduced in TRH-treated rats (p < 0.01) but the relative amount of basal and stimulated amylase discharge (% of total) was not influenced by TRH. Blood TRH levels were significantly increased (324 ± 53 vs. 48 ± 6 fmol/ml,p< 0.01) 12 h after the last TRH administration. These data indicate that chronic TRH administration in rats induces pancreatic hyperplasia but decreases the pancreatic concentration of digestive enzymes. The increase of TRH blood concentrations over a prolonged period of time in the treated group might be explained by a downregulation of the TRH degradation system.
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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6. |
A Novel Assay for Pancreatic Cellular DamageIV. Serum Concentrations of Pancreas‐Specific Protein (PASP) in Acute Pancreatitis and Other Abdominal Diseases |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 42-49
Roland Fernstad,
Åke Pousette,
Kjell Carlström,
Holger Sköldefors,
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摘要:
Pancreas-specific protein (PASP) was compared with serum amylase in 95 episodes of acute pancreatitis with the diagnoses supported by elevated amylase levels. The etiology was typical for Scandinavian countries, with alcohol as the predominant factor, followed by cholelithiasis. PASP values were clearly raised in all patients, except in three cases found to have high salivary-type amylase levels, and one patient with recurrent alcohol pancreatitis. The rise of PASP levels were in general more pronounced than the corresponding amylase elevations, especially in severe pancreatitis. The elevations were generally parallel for the two analytes, but in 41% of the cases PASP levels remained elevated 2–11 days longer than the corresponding amylase levels. PASP was, however, eliminated from the circulation at a rate comparable to that of amylase. The serum range of PASP for 259 healthy subjects was 15–111 μg/L with 95% of the values within 16–98 μg/L. The upper reference level was set at 100 kg/L. PASP levels were also determined for 291 patients with disorders other than acute pancreatitis. Serum levels in patients with renal insufficiency (n = 12), primary biliary cirrhosis (n = 9), and diabetes mellitus (n = 17) were equal to those in healthy subjects. Eight patients of 173 with acute abdominal disorders and no evidence of pancreatitis had elevated PASP levels as well as 4 patients with prostatic carcinoma (n = 28) and 2 patients with benign prostatic hyperplasia (n = 16). PASP values were low in chronic painful pancreatitis (n = 15) and pancreatic cancer (n = 11).
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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7. |
Carbamylcholine and Phorbol Esters Desensitize Muscarinic Receptors by Different Mechanisms in Rat Pancreatic Acini |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 50-59
Louise Blanchard,
Brigitte Paquette,
Louise Larose,
Jean Morisset,
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摘要:
Pretreatment of rat pancreatic acini with phorbol 12-myristate, 13-acetate (PMA), a protein kinase C (PK-C) activator, caused the desensitization of carbamylcholine (CBC)-induced amylase release in a concentration- and time-dependent fashion. The less potent phorbol-12, 13-dibutyrate (PDBu) also provoked a desensitization, but the inactive 4-α-phorbol-12,13-didecanoate had no effect. PMA or PDBu also significantly reduced subsequent amylase release induced by caerulein or secretin in contrast to CBC, which only reduced amylase release induced by CBC or secretin. Preincubation of acini with PMA did not lead to a decrease in PMA or A23187-stimulated amylase release. A 3 h resting period did not restore the desensitization induced by PMA or PDBu. Pretreatment with PMA did not cause changes in muscarinic receptor high- and low-affinity populations as observed with CBC pretreatment. The PK-C inhibitor H-7 completely prevented the desensitization induced by PDBu but not that induced by CBC. TMB-8, another PK-C inhibitor, also completely prevented the desensitization induced by PDBu but only partially that induced by CBC. These results suggest that phorbol esters can induce desensitization of muscarinic receptor-stimulated amylase release by a different mechanism than that involved in muscarinic agonist-induced desensitization.
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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8. |
The Effect of CR 1409, A Potent CCK Receptor Antagonist, on Basal and Stimulated Pancreatic Secretion in Rat |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 60-64
T. Takács,
I. Nagy,
Á. Pap,
V. Varró,
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摘要:
The effect of a specific cholecystokinin (CCK) receptor blocker from Rotta Research Laboratorium (MonzaMilano, Italy), CR 1409 (Lorglumide), on pancreatic secretion was investigated. CR 1409 caused a rightward and parallel shift in the dose-response curve of CCK-8-stimulated pancreatic protein secretion in anesthetized rats, demonstrating a competitive mechanism of inhibition. The mean PA, value, showing the 50% inhibitory dose of CR 1409, was 6.4. CR 1409 proved to be about 1,000 times more potent as a CCK receptor blocker than proglumide, the first glutaramic acid analogue with anti-CCK potential. In conscious rats, pancreatic protein and water secretion were significantly diminished for about 2 h in response to 300 μg/kg of CR 1409 given subcutaneously during diversion of pancreatic juice, demonstrating inhibition of endogenous CCK by this new glutaramic acid derivative. By contrast, during reintroduction of precollected pancreatic juice into the duodenum, when the release of CCK is almost totally eliminated, pancreatic secretion was not modified by the same dose.
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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9. |
Evaluation of Tests of Exocrine and Endocrine Pancreatic in Function in Older Patients with Cystic Fibrosis |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 64-69
Cornelis Lamers,
Jan M. J. Jansen,
Jan Hafkenscheid,
Cees Jongerius,
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摘要:
In order to determine the value of noninvasive tests in the analysis of pancreatic function in cystic fibrosis, 14 older cystic fibrosis patients were studied by a set of noninvasive tests of exocrine and endocrine pancreatic function. The tests, comprising trypsin, total amylase, pancreatic isoamylase, lipase, pancreatic polypeptide (PP), glucose and insulin in fasting serum, PP, glucose and insulin in postprandial serum, and p-aminobenzoic acid (PABA) excretion in urine, were compared to fecal fat excretion after discontinuation of pancreatic enzyme supplementation. Eleven of the 14 patients were found to have a fecal fat excretion of more than 7 g/day. Serum levels of trypsin, pancreatic isoamylase and lipase, and the urinary excretion of PABA showed significant negative correlations with fecal fat excretion. Endocrine pancreatic function was abnormal in the majority of patients with fibrocystic disease. Although serum trypsin, postprandial PP, and urinary PABA excretion were the most sensitive tests for severe exocrine pancreatic insufficiency, the differences in sensitivity were rather modest. Therefore, the type of test to be selected for clinical use is mainly dependent upon factors as accessibility, simplicity, patient's acceptability, and costs.
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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10. |
Rat and Porcine Galanin Are Equipotent in Inhibiting Insulin Responses to Glucose in the Anesthetized Rat |
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Pancreas,
Volume 5,
Issue 1,
1990,
Page 70-74
Evelyn Schnuerer,
Åke Rökaeus,
Mats Carlquist,
Tomas Bergman,
John Dupré,
Thomas McDonald,
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摘要:
The structure of rat galanin, recently elucidated using recombinant DNA technology, differs from porcine galanin by three amino acid residue substitutions at positions located in the C-terminal region. A synthetic replicate of the proposed structure of rat galanin was prepared and its potency to inhibit insulin responses to glucose in anesthetized rats was compared with that of porcine galanin. Within experimental error, the dose-response curves of porcine and rat galanin to inhibit glucose-stimulated rat insulin responses were indistinguishable. The ED., dose of porcine galanin was 0.6 μg/100 g body weight and for rat galanin 0.8 μg/100 g body weight. These results suggest that the C-terminal region of the molecule is not essential for galanin's potent inhibitory action on insulin responses to glucose administration.
ISSN:0885-3177
出版商:OVID
年代:1990
数据来源: OVID
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